An extract of <i>Galtonia regalis</i> from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC<sub>50</sub> value less than 1.25 μg/mL. The two known cholestane glycosides <b>1</b> and <b>2</b> and the five new cholestane glycosides galtonosides A-E (<b>3</b>-<b>7</b>) were isolated after bioassay-directed fractionation. The structures of the new compounds were determined by interpretation of their NMR and mass spectra. Among these compounds, galtonoside B (<b>4</b>) displayed the most potent antiplasmodial activity, with an IC<sub>50</sub> value of 0.214 μM against the drug-resistant Dd2 strain of <i>Plasmodium falciparum</i>.